Adenosine deaminase deficiency (ADA) is an inherited condition that affects the immune system and typically leads to severe combined immunodeficiency (SCID). People with SCID have a reduced or absent immune response which leaves them vulnerable to frequent bacterial, viral, and fungal infections. Most people affected by ADA develop symptoms of the condition before 6 months of age. However, approximately 10-15% of affected people have a "delayed" onset of symptoms; diagnosis of these cases, which are often less severe, typically takes place later in childhood (often between age 1 and 10) or even into adulthood. Signs and symptoms of ADA include pneumonia, chronic diarrhea, widespread skin rashes, slowed growth and/or developmental delay. ADA is caused by changes (mutations) in the ADAgene and is inherited in an autosomal recessive manner.[1][2] The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person.[3][8061

In most cases, signs and symptoms of adenosine deaminase deficiency (ADA) develop before 6 months of age. These affected babies are usually diagnosed with severe combined immunodeficiency (SCID), a condition characterized by a reduced or absent immune response. Babies with SCID are vulnerable to frequent bacterial, viral, and fungal infections. Although many of these infections would cause no illness or only mild disease in healthy children, they can be very severe and even life-threatening in children with SCID. Signs and symptoms of SCID include chronic diarrhea; pneumonia and other lung infections; widespread skin rashes; slowed growth; absent tonsils and lymph nodes; bone abnormalities; and/or developmental delay.[2][4]

Approximately 10-15% of affected people have a "delayed" onset of symptoms, which typically develop later in childhood (often between age 1 and 10) or even into adulthood. In these cases, people are usually diagnosed with "combined immunodeficiency (CID)" since signs and symptoms are initially milder than those seen in SCID. However, the immune response becomes more damaged the longer the condition goes undiagnosed.[2] Over time, these affected people may develop chronic lung damage, malnutrition, and other health problems.[2][1]

Last updated: 1/5/2015

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition.
Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency).
Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Adenosine deaminase deficiency is caused by changes (mutations) in the ADAgene. This gene encodes an enzyme that is found in the lymphocytes (specialized white blood cells), which are an important part of the immune system and help protect the body from infections. The function of this enzyme is to convert a substance that is harmful to lymphocytes (called deoxyadenosine) to a non-toxic material. Mutations in the ADA gene cause this enzyme to have reduced or absent function, allowing deoxyadenosine to buildup in the lymphocytes. This results in the loss of lymphocytes before they are able to mature and fight infection, leading to severe combined immunodeficiency.[1]

Adenosine deaminase deficiency is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Yes, genetic testing is available for ADA, the gene known to cause adenosine deaminase deficiency.[2]Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Last updated: 1/5/2015

In some states of the United States, newborns are screened for various conditions that can cause severe combined immunodeficiency, including adenosine deaminase deficiency (ADA). In the absence of newborn screening, ADA is typically suspected in people with frequent infections and other characteristic symptoms. The diagnosis can be confirmed by blood tests that demonstrates the following:[2][5]

Other tests that are helpful in establishing a diagnosis include x-rays that show ADA-associated bone abnormalities and genetic testing that identifies a change (mutation) in each copy of the ADA gene.[2][5]

Last updated: 1/5/2015

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.

Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.

US National Newborn Screening Status Report (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

It is also important to restore the function of the immune system, if possible. The most effective treatment is transplantation of blood-forming stem cells from the bone marrow of a healthy person (called bone marrow transplant/stem cell transplant or BMT/SCT). This therapy cures the condition in approximately 70% or more of people with severe combined immunodeficiency (SCID), including those affected by ADA. If a BMT/SCT is not an option, enzyme replacement therapy (ERT) may be recommended. ERT is a treatment that replaces the enzyme that is missing or not working properly (adenosine deaminase) with a synthetic form of the enzyme.[2][5][6]

For more information about the treatment and management of ADA, please click here.

The long-term outlook (prognosis) for people with adenosine deaminase deficiency (ADA) varies depending on the severity of the condition, the timing of the diagnosis and the response to treatment. For example, without early diagnosis and treatment, babies with ADA usually do not survive past age 2.[1][2] However, if bone marrow transplant/stem cell transplant (transplantation of blood-forming stem cells from the bone marrow of a healthy person) is effective, the prognosis is typically good.[5]

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Adenosine deaminase deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Adenosine deaminase deficiency. This website is maintained by the National Library of Medicine.

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.

The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.

Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.

Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

PubMed is a searchable database of medical literature and lists journal articles that discuss Adenosine deaminase deficiency. Click on the link to view a sample search on this topic.

NCATS Co-Sponsored Conferences

Description: The major goals of this conference were to disseminate novel, unpublished results; identify new technologies and clinical therapies; and foster new collaborations among participants. A hallmark of this conference is the exceptionally broad cross-section of participants in terms of research focus (basic, translational, and clinical), age (the large meeting venue draws many younger scientists, graduate students, and senior investigators; ASM committed $20,000 to subsidize graduate student travel), institutional affiliation (academia, government, private industry, and publishing), and geography. Numerous opportunities were provided for in-depth discussion during and after sessions and at meals, including the popular evening poster sessions to promote informal interactions among all participants.

Contact:
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